Gastroenterology: Pancreas and Biliary

• Gallbladder and bile ducts: Gallstones | Bile Duct Stones and Gallstone Complications | Problems After Cholecystectomy | Gallbladder Polyps and Cancer | Cholangiocarcinoma | Other Biliary Conditions
• Pancreas: Chronic Pancreatitis | Pancreatic Exocrine Insufficiency | Autoimmune Pancreatitis and IgG4-related Disease | Pancreatic Cancer | Pancreatic Cysts | Inherited Pancreatic Disease
• Procedures: ERCP, EUS and Biliary Stents
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🟡 The pancreas and biliary tree produce two of the commonest surgical problems (gallstones and pancreatitis) and two of the deadliest cancers (pancreatic cancer and cholangiocarcinoma). Acute pancreatitis, acute cholecystitis and cholangitis are covered in the Gastroenterology Emergencies chapter; this chapter covers the rest.
Your four questions for every patient: Is this pain biliary, pancreatic or something else? Is there jaundice - and is it painless? Is the pancreas still working (digestion and glucose control)? Could this be cancer, and does the patient need an urgent CT?

Gallstones

What they are: Stones formed in the gallbladder, mostly cholesterol stones. Pigment stones occur in haemolysis (e.g. sickle cell disease, hereditary spherocytosis) and cirrhosis. About 1 in 10 UK adults have gallstones; most never have symptoms.

Risk factors (the "5 Fs" - female, fat, fertile, forty, fair - are a rough guide):

• Female sex; pregnancy; oestrogens.
• Obesity; rapid weight loss (including after bariatric surgery).
• Older age; family history.
• Diabetes.
• Crohn's disease or ileal resection.
• Drugs - octreotide, fibrates, ceftriaxone.
• Long-term parenteral nutrition.
• Haemolysis.

Symptoms:

• Biliary colic:
  • Severe constant pain in the right upper quadrant or epigastrium, sometimes spreading to the right shoulder blade.
  • Often after fatty meals or at night.
  • Lasts 30 minutes to a few hours.
  • No fever; normal blood tests.
• Bloating and indigestion are not reliably caused by gallstones.

Diagnosis: Abdominal ultrasound (stones with acoustic shadowing). Check LFTs and amylase or lipase.

Management (NICE CG188):

• No symptoms, normal gallbladder: Reassure - no treatment needed.
• Symptomatic gallbladder stones: Laparoscopic cholecystectomy.
• Acute cholecystitis: Laparoscopic cholecystectomy within 1 week of diagnosis (see the Gastroenterology Emergencies chapter).
• Gallstone pancreatitis: Cholecystectomy during the same admission, or within 2 weeks, to prevent recurrence.
• Ursodeoxycholic acid can dissolve small cholesterol stones, but it is slow and they recur - rarely used.
• Frail patients: Percutaneous cholecystostomy drain for cholecystitis; ERCP and sphincterotomy for bile duct stones.

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Bile Duct Stones and Gallstone Complications

Common bile duct stones (choledocholithiasis):

• Features: Biliary pain with obstructive jaundice (dark urine, pale stools), and cholestatic or very high ALT. May cause cholangitis or pancreatitis.
• Imaging (NICE CG188):
  • Ultrasound first - it often misses duct stones but shows a dilated duct.
  • MRCP if ultrasound is not diagnostic but the duct is dilated or LFTs are abnormal.
  • EUS if MRCP is inconclusive.
• Treatment: Clear the duct - ERCP with sphincterotomy and stone extraction, or surgical duct exploration during cholecystectomy - then cholecystectomy.

Other gallstone complications:

• Mirizzi syndrome: A stone in the neck of the gallbladder (Hartmann's pouch) presses on the common hepatic duct, causing jaundice. Surgery is difficult.
• Gallstone ileus:
  • A large stone erodes from the gallbladder into the duodenum and blocks the terminal ileum.
  • Usually in older women.
  • Rigler's triad on imaging: small bowel obstruction, air in the biliary tree (pneumobilia), and an ectopic stone.
  • Treated with surgery (enterolithotomy).
• Empyema (pus-filled gallbladder) and gangrenous or perforated gallbladder - complications of cholecystitis, often in older people and people with diabetes.
• Bouveret syndrome: A stone blocks the duodenum, causing gastric outlet obstruction.
• Gallbladder cancer - long-standing gallstones are a risk factor.

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Problems After Cholecystectomy

• Early problems:
  • Bile leak (from the cystic duct stump or small ducts) - pain, fever, fluid collection. Treat with ERCP and a stent.
  • Bile duct injury (about 1 in 300–500 operations) - jaundice or leak; refer to a specialist hepatobiliary unit.
  • Retained bile duct stones.
• Later problems:
  • Bile acid diarrhoea - common; responds to colestyramine (see the Bowel Disorders chapter).
  • Recurrent bile duct stones.
  • Functional biliary sphincter disorder (formerly sphincter of Oddi dysfunction) - biliary-type pain without stones. Sphincterotomy is not recommended without objective findings (high ERCP pancreatitis risk).
  • Persisting symptoms that were never biliary - IBS, functional dyspepsia, peptic ulcer.

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Gallbladder Polyps and Cancer

Gallbladder polyps - usually found by chance on ultrasound. Most are cholesterol polyps (harmless). Management follows European guidance (ESGAR/EAES 2022):

• 10 mm or more: Cholecystectomy (risk of cancer).
• 6–9 mm: Cholecystectomy if there are risk factors (age over 60, PSC, Indian ethnicity, flat/sessile shape); otherwise ultrasound follow-up.
• 5 mm or less, with no risk factors: No follow-up needed.
• Growth of 2 mm or more on follow-up - consider surgery.
• PSC: Cholecystectomy for polyps of 8 mm or more.

Gallbladder cancer:

• Risk factors:
  • Long-standing gallstones.
  • Porcelain gallbladder (calcified wall).
  • Polyps.
  • PSC; pancreaticobiliary maljunction.
  • Commoner in women and in South America and India.
• Often found by chance after cholecystectomy, or late with jaundice, pain and weight loss.
• Treatment: Radical surgery for early disease (re-resection if found incidentally); chemotherapy for advanced disease. Poor prognosis overall.

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Cholangiocarcinoma

What it is: Cancer of the bile duct lining. It can be:

• Intrahepatic - inside the liver.
• Perihilar - at the junction of the right and left hepatic ducts ("Klatskin tumour").
• Distal - in the common bile duct.

Risk factors:

• Primary sclerosing cholangitis (the main UK risk).
• Choledochal cysts.
• Liver flukes (Clonorchis, Opisthorchis - South East Asia).
• Bile duct stones in the liver.
• Cirrhosis; hepatitis B and C; MASLD.
• Many have no risk factor.

Symptoms:

• Painless obstructive jaundice.
• Itch.
• Weight loss.
• Cholangitis.
• Intrahepatic tumours often present late with pain or as a liver mass.

Diagnosis:

• CT and MRCP (stricture and level).
• CA19-9 (also raised by cholangitis and any biliary obstruction).
• ERCP with brushings, cholangioscopy, or EUS-guided biopsy - tissue can be hard to get.
• In PSC, distinguishing a benign stricture from cancer is difficult - specialist centre.

Treatment:

• Surgery is the only cure, but fewer than 1 in 4 tumours are resectable. Adjuvant capecitabine afterwards.
• Advanced:
  • Gemcitabine and cisplatin with durvalumab (or pembrolizumab).
  • Molecular testing - targeted drugs for FGFR2 fusions (pemigatinib) and IDH1 mutations (ivosidenib).
• Biliary drainage - stents by ERCP or percutaneously - for jaundice, itch and cholangitis.
• Transplant for selected early perihilar tumours (specialist protocols).

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Other Biliary Conditions

• Choledochal cysts:
  • Congenital dilatation of the bile ducts.
  • Present with pain, jaundice, a mass, cholangitis or pancreatitis - in childhood or adulthood.
  • Cancer risk - excision with hepaticojejunostomy.
  • Caroli disease - dilatation of the ducts inside the liver.
• Ampullary tumours:
  • Adenomas or cancers at the ampulla of Vater (where the bile and pancreatic ducts enter the duodenum). Linked to FAP.
  • They cause jaundice early, so they are often found at a curable stage - endoscopic ampullectomy or Whipple's procedure.
• Benign biliary strictures: After surgery or chronic pancreatitis, PSC, IgG4 disease. Treated with ERCP stents or surgery.
• Biliary parasites: Ascaris and liver flukes - biliary colic, cholangitis, pancreatitis in travellers and migrants.
• HIV cholangiopathy: Opportunistic infections (CMV, cryptosporidium) in advanced HIV.
• Ischaemic cholangiopathy: After liver transplant (hepatic artery thrombosis) or after critical illness ("secondary sclerosing cholangitis in critically ill patients").

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Chronic Pancreatitis

What it is: Long-term inflammation that permanently scars the pancreas, causing pain, loss of digestive enzymes (exocrine failure) and diabetes (endocrine failure).

Causes (TIGAR-O):

• Alcohol (the commonest in the UK).
• Smoking (a major independent cause, and it speeds progression).
• Genetic - PRSS1, SPINK1, CFTR.
• Autoimmune.
• Recurrent acute pancreatitis.
• Obstruction - duct strictures, tumours, pancreas divisum.
• Hypercalcaemia; high triglycerides.
• Idiopathic.

Features:

• Epigastric pain spreading to the back, often worse after eating; eased by leaning forward.
• Steatorrhoea and weight loss (exocrine failure).
• Diabetes (type 3c).
• Pain may lessen as the gland "burns out".

Diagnosis:

• CT - pancreatic calcification, duct dilatation, atrophy.
• MRCP or EUS for early changes.
• Faecal elastase (exocrine function).
• HbA1c.
• Amylase and lipase are often normal.

Management:

• Stop alcohol and smoking - this slows progression and reduces pain.
• Pain:
  • Simple analgesia first; tricyclics or gabapentinoids for nerve pain.
  • Try to avoid long-term opioids (dependence, opioid-induced hyperalgesia).
  • Endoscopic therapy (stones broken with shock waves, duct stents) or surgery (drainage or resection) for duct obstruction - earlier surgery may relieve pain better.
  • Coeliac plexus block (short-lived benefit).
• Pancreatic enzyme replacement (see below).
• Diabetes:
  • Often needs insulin.
  • Hypoglycaemia risk - glucagon is also lost - especially if drinking.
  • Metformin can be used first.
• Nutrition: Dietitian review. Fat-soluble vitamins (A, D, E, K).
• Bone health: High osteoporosis risk - DEXA.

Complications:

• Pseudocysts.
• Splenic vein thrombosis - causing gastric varices.
• Bile duct or duodenal stricture.
• Pseudoaneurysm (bleeding).
• Pancreatic cancer (risk raised about 10–15 times).

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Pancreatic Exocrine Insufficiency

What it is: The pancreas doesn't make enough digestive enzymes, so fat (and protein) isn't absorbed.

Causes:

• Chronic pancreatitis.
• Pancreatic cancer (very common).
• Pancreatic surgery.
• Cystic fibrosis.
• Severe acute pancreatitis.
• Diabetes (long-standing).
• After gastric surgery.
• Coeliac disease.
• Older age.

Symptoms:

• Pale, greasy, foul-smelling stools that float or are hard to flush.
• Bloating and wind.
• Weight loss.
• Fat-soluble vitamin deficiency.

Diagnosis:

• Faecal elastase under 200 µg/g (under 100 is severe). Watery stools can give a falsely low result.
• A treatment trial is reasonable where the cause is clear (e.g. pancreatic cancer).

Treatment - pancreatic enzyme replacement therapy (PERT):

• Creon (pancrelipase) - start at about 50,000 lipase units with each meal and 25,000 with snacks. Increase according to symptoms (often 75,000 or more per meal).
• Take it with the first mouthful of food (or spread through the meal). Don't chew or crush the capsules; they can be opened onto acidic food.
• Add a PPI if the response is poor (acid inactivates the enzymes).
• Don't restrict fat - eat a normal diet with enough enzymes.
• It is pork-derived - discuss with patients for religious or ethical reasons; there is no non-porcine alternative.
• Offer PERT to everyone with unresectable pancreatic cancer (NICE NG85) - it improves weight and quality of life.
• Check vitamin D and other fat-soluble vitamins; DEXA.

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Autoimmune Pancreatitis and IgG4-related Disease

• Type 1 autoimmune pancreatitis - the pancreatic form of IgG4-related disease:
  • Usually older men.
  • Painless obstructive jaundice and weight loss - it mimics pancreatic cancer.
  • CT: a diffusely swollen "sausage-shaped" pancreas with a rim ("halo").
  • Raised serum IgG4 (not in everyone, and also raised in some cancers).
  • Other organs:
    • IgG4-related sclerosing cholangitis.
    • Swollen salivary and tear glands (Mikulicz disease).
    • Retroperitoneal fibrosis.
    • Aortitis.
    • Kidney disease.
    • Riedel's thyroiditis.
    • Orbital disease.
• Type 2 autoimmune pancreatitis: Younger people; linked to IBD; IgG4 is normal.
• Diagnosis:
  • Imaging; IgG4 level; other organ involvement.
  • EUS-guided biopsy - always exclude cancer.
  • Response to steroids supports the diagnosis.
• Treatment:
  • Prednisolone (e.g. 30–40 mg daily for about 4 weeks, then taper) - usually a rapid response.
  • Biliary stent if jaundiced.
  • Relapse is common - maintenance azathioprine or rituximab.
  • Watch for diabetes (from both the disease and steroids).

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Pancreatic Cancer

What it is: Usually ductal adenocarcinoma, most often in the head of the pancreas. It is the UK's fifth biggest cancer killer and has the lowest survival of common cancers (under 10% at 5 years), because it presents late.

Risk factors:

• Smoking.
• Older age.
• Obesity.
• Long-standing diabetes, and new-onset diabetes (can be an early sign).
• Chronic pancreatitis.
• Alcohol.
• Family history and inherited syndromes - BRCA2, PALB2, Lynch, Peutz–Jeghers, familial atypical multiple mole melanoma (CDKN2A), hereditary pancreatitis.
• Some pancreatic cysts (IPMN).

Symptoms:

• Painless obstructive jaundice (head tumours) - dark urine, pale stools, itch.
• Courvoisier's law: A palpable gallbladder with painless jaundice is unlikely to be due to gallstones.
• Weight loss, anorexia.
• Epigastric pain spreading to the back (body and tail tumours).
• New diabetes in an older person, especially with weight loss.
• Steatorrhoea.
• Vomiting (duodenal obstruction).
• Migratory thrombophlebitis (Trousseau's sign); VTE.

Referral (NICE NG12):

• Age 40 or over with jaundice - suspected cancer pathway referral.
• Age 60 or over with weight loss plus any of: diarrhoea, back pain, abdominal pain, nausea, vomiting, constipation, or new-onset diabetes - urgent direct-access CT within 2 weeks.

Diagnosis and staging (NICE NG85):

• Pancreatic protocol CT (chest, abdomen, pelvis).
• PET-CT if resection is possible.
• EUS with biopsy.
• CA19-9 (follow-up - not for diagnosis; also raised by jaundice).
• Germline genetic testing is offered (e.g. BRCA) - it affects treatment and family screening.

Treatment (pancreatic MDT):

• Resectable (about 15–20%):
  • Surgery - pancreaticoduodenectomy (Whipple's) for head tumours; distal pancreatectomy for tail tumours.
  • Then adjuvant chemotherapy - modified FOLFIRINOX if fit, or gemcitabine with capecitabine.
  • Avoid routine pre-operative biliary stenting unless surgery is delayed or the patient has cholangitis.
• Borderline resectable: Chemotherapy first (neoadjuvant), then surgery if possible.
• Locally advanced or metastatic:
  • Chemotherapy (FOLFIRINOX, gemcitabine with nab-paclitaxel).
  • Olaparib maintenance for BRCA mutations.
• Palliation:
  • Metal biliary stent (ERCP) for jaundice.
  • Duodenal stent or bypass for vomiting.
  • PERT for everyone; dietitian.
  • Pain control, including coeliac plexus block.
  • VTE treatment (LMWH or DOAC).
  • Manage diabetes.
• Surveillance (EUS or MRI) is offered to some high-risk families in research or specialist programmes.

Pancreatic neuroendocrine tumours (insulinoma, gastrinoma and non-functioning tumours) - see the NETs and Hypoglycaemia chapter.

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Pancreatic Cysts

Pancreatic cysts are found on more than 1 in 10 scans in older people. Most are benign, but some are precancerous. Management follows the European evidence-based guidelines (2018).

Worrying features - consider surgery:

• Jaundice from the cyst.
• An enhancing solid component (5 mm or more).
• Main pancreatic duct 10 mm or more.
• Positive cytology.

Relative indications for surgery:

• Growth of 5 mm or more a year.
• Cyst 4 cm or larger.
• Main duct 5–9.9 mm.
• Raised CA19-9.
• New diabetes.
• Pancreatitis.

Tests:

• MRI/MRCP.
• EUS with fluid aspiration - high CEA suggests a mucinous cyst; check cytology.
• Surveillance only if the patient would be fit for surgery.

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Inherited Pancreatic Disease

• Hereditary pancreatitis (PRSS1 mutation, autosomal dominant):
  • Recurrent acute pancreatitis from childhood, leading to chronic pancreatitis.
  • High lifetime pancreatic cancer risk (especially in smokers) - consider surveillance; never smoke.
• SPINK1 and CFTR variants - increase the risk of recurrent and chronic pancreatitis.
• Cystic fibrosis:
  • Most patients have pancreatic exocrine insufficiency from birth (PERT is essential).
  • CF-related diabetes.
  • CF liver disease (focal biliary cirrhosis).
  • Distal intestinal obstruction syndrome.
  • CFTR modulators (e.g. elexacaftor/tezacaftor/ivacaftor) have improved outcomes.
• Shwachman–Diamond syndrome: Pancreatic insufficiency with bone marrow failure and skeletal changes (children).
• Pancreas divisum: A common developmental variant (ducts don't fuse). Usually harmless; occasionally linked to recurrent pancreatitis.
• Annular pancreas: Pancreas encircling the duodenum - duodenal obstruction in babies (linked to Down syndrome).

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ERCP, EUS and Biliary Stents

• ERCP (endoscopic retrograde cholangiopancreatography):
  • A therapeutic procedure - remove stones, place stents, take brushings. Use MRCP or EUS for diagnosis.
  • Risks:
    • Post-ERCP pancreatitis (about 3–5%) - reduced by giving rectal diclofenac or indometacin 100 mg, IV fluids, and pancreatic stents in high-risk cases.
    • Bleeding (after sphincterotomy).
    • Perforation.
    • Cholangitis.
• EUS (endoscopic ultrasound):
  • Detailed images of the pancreas and bile duct.
  • Fine-needle biopsy.
  • Cyst aspiration.
  • Drainage of collections.
  • Coeliac plexus block.
  • EUS-guided biliary drainage when ERCP fails.
• Biliary stents:
  • Plastic stents - temporary (block after about 3 months).
  • Self-expanding metal stents - longer lasting; used for malignant strictures.
  • A blocked stent presents with jaundice, fever and cholangitis - antibiotics and urgent stent change.
• PTC (percutaneous transhepatic cholangiography) - drainage through the liver when ERCP isn't possible (e.g. hilar tumours, after gastric bypass).
• Before procedures: Check clotting and platelets; manage anticoagulants (see the GI Investigations and Nutrition chapter); give antibiotic prophylaxis in some cases (e.g. incomplete drainage, PSC, after transplant).

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Drug Reference Table

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Spot the Diagnosis

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Exam-style Scenarios

1. A 45-year-old woman has had three episodes of biliary colic. Ultrasound shows gallstones and a normal duct.
Answer: Symptomatic gallstones - offer laparoscopic cholecystectomy.

• Low-fat diet while waiting.
• Return urgently if fever, jaundice or persistent pain develops.

2. A 68-year-old man has painless jaundice, dark urine and 6 kg weight loss.
Answer: Suspected pancreatic or distal bile duct cancer.

• Suspected cancer pathway referral; pancreatic protocol CT.
• EUS with biopsy; CA19-9; MDT discussion.
• If resectable: Whipple's (avoid routine pre-operative stenting).
• If not: metal stent, chemotherapy if fit, PERT, palliative care.

3. A 52-year-old man with alcohol-related chronic pancreatitis has greasy stools and weight loss.
Answer: Pancreatic exocrine insufficiency.

• Faecal elastase; Creon about 50,000 units with meals and 25,000 with snacks, titrated; add a PPI if needed.
• Check HbA1c, vitamin D and fat-soluble vitamins; DEXA.
• Support stopping alcohol and smoking.

4. A CT for back pain in a 74-year-old woman shows a 2.2 cm branch-duct IPMN with no worrying features.
Answer: Low-risk branch-duct IPMN.

• MRI surveillance if she would be fit for surgery.
• Consider surgery if worrying features develop (enhancing nodule, main duct 10 mm or more, jaundice, rapid growth).

5. An ultrasound in a 40-year-old shows a 7 mm gallbladder polyp. She has no risk factors.
Answer: Ultrasound follow-up (e.g. at 6 months, 1 year and 2 years).

• Cholecystectomy if it grows by 2 mm or more, or reaches 10 mm.
• Earlier surgery if she had risk factors (PSC, age over 60, sessile polyp).

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Key Points

• Asymptomatic gallstones need no treatment; symptomatic stones need laparoscopic cholecystectomy.
• Cholecystectomy within 1 week for acute cholecystitis, and in the same admission for gallstone pancreatitis.
• Suspected duct stones: ultrasound, then MRCP, then EUS; ERCP is for treatment.
• Gallstone ileus: Rigler's triad - obstruction, pneumobilia, ectopic stone.
• Gallbladder polyps of 10 mm or more need cholecystectomy.
• PSC is the main UK risk factor for cholangiocarcinoma.
• Chronic pancreatitis: alcohol and smoking - stop both. CT shows calcification; amylase is often normal.
• Type 3c diabetes carries a high hypoglycaemia risk.
• PERT: about 50,000 units with meals and 25,000 with snacks, with the first mouthful; add a PPI if poor response; give to all with unresectable pancreatic cancer.
• Autoimmune pancreatitis mimics cancer - sausage pancreas, high IgG4, other organ disease; steroids, but exclude cancer first.
• Pancreatic cancer: painless jaundice, weight loss, back pain, new diabetes in older people. Urgent CT at 60 or over with weight loss plus symptoms.
• Mucinous cysts (IPMN, MCN) can become cancer; serous cystadenomas are benign.
• Rectal NSAIDs reduce post-ERCP pancreatitis.

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Guidelines and Further Reading

• NICE CG188: Gallstone disease - diagnosis and management
• NICE NG85: Pancreatic cancer in adults - diagnosis and management
• NICE NG12: Suspected cancer - recognition and referral
• NICE NG104: Pancreatitis (acute and chronic)
• European evidence-based guidelines on pancreatic cystic neoplasms (2018)
• ESGAR/EAES/EFISDS/ESGE guidance on gallbladder polyps (2022)
• BSG guidelines on the diagnosis and management of cholangiocarcinoma (2023)
• UK guidelines for the management of pancreatic exocrine insufficiency (Pancreatic Society of Great Britain and Ireland)
• Pancreatic Cancer UK
• BNF - for current doses

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